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This interdisciplinary symposium will convene leading experts in adult stem cell research, tissue regeneration and bioengineering to discuss cutting edge research at the intersection of these disciplines, with the overall aim of translating current stem cell knowledge into clinical applications.

Grantsmanship for Students and Postdocs: Pathways to Individual Fellowship

March 20, 2019

Join Science Alliance for “Grantsmanship for Graduate Students and Postdocs” to learn the skills for concise and persuasive writing that is not only vital in academia, but essential for any career path.

This two-day symposium will convene leading experts in cancer immunotherapy to discuss cutting-edge findings in the broad area of combination therapies, including checkpoint inhibitors and cellular therapies. Particular emphasis will be given to the biological mechanisms underlying combination hypotheses, bispecific antibodies and other emerging modalities for delivery of combination therapies, as well as a discussion of the importance of effective clinical trial design.

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Join Dr. Rebecca Nebel from the Society for Women’s Health Research and the Science Alliance to learn more about how to utilize informational interviews for career exploration, networking, and finding the job of your dreams.

Join us at the Academy to learn directly from a PhD hiring manager what they look for in a resume, the best way to communicate technical and transferable skills to a mixed audience, and how to showcase not just what you do but who you are and why an employer should want to hire you.

This panel will highlight the realities of a career change and the opportunities available to scientists who are thinking about a career in teaching. Our guests will discuss what it’s really like to teach in public schools, the shift in culture from a lab to a classroom, and the programs that will help prepare you to get there.

The Junior Academy recruits STEM experts to coach teams of talented, highly motivated students as they compete in science & technology challenges sponsored by industry-leading companies. Students and mentors can participate from anywhere in the world, connecting with one another via Launchpad, our interactive challenge platform.

Available exclusively to our Member community, Member-to-Member Mentoring is a self-directed mentoring program that matches early career scientists and engineers with experienced STEM professionals for advice and coaching.

In this Annals issue, leading scientists and scholars explore the question of meaning through the lens of scientific inquiry, using interdisciplinary approaches to examine the various sources from which we might derive greater insight into the meaning and purpose of human existence.

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For 200 years—since 1817—the Academy has brought together extraordinary people working at the frontiers of discovery. Among the oldest scientific organizations in the United States, it has become not only an enduring cultural institution in New York, but also one of the most significant organizations in the global scientific community.

Pancreatic Cancer: Translation of New Ideas

Recent years have witnessed remarkable developments in our understanding of pancreatic ductal adenocarcinoma, and many new concepts are beginning to be translated into novel therapeutic approaches. Though pancreatic cancer remains one of the deadliest cancers, work on the fundamental biological programs that drive the disease has yielded insights into the importance of stromal cells within the tumor, the behavior the neoplastic epithelial cells, and the paracrine signals that tie them together. This symposium will cover the latest research developments in pancreatic cancer, with a focus on preclinical and early clinical investigations of rationally targeted drugs that were translated from basic science observations.

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Please note: Transmission of presentations via the webinar is subject to individual consent by the speakers. Therefore, we cannot guarantee that every speaker's presentation will be broadcast in full via the webinar. To access all speakers' presentations in full, we invite you to attend the live event in New York City where possible.

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Agenda

* Presentation times and titles are subject to change.

Friday October 12, 2012

12:00 PM

Welcome and IntroductionJennifer Henry, PhD, The New York Academy of SciencesKenneth P. Olive, PhD, Columbia University Medical Center

Speakers

Organizers

Kenneth P. Olive, PhD

Columbia University Medical Center

Dr. Kenneth P. Olive began his doctoral studies in 1998 with Tyler Jacks at the MIT Center for Cancer Research, investigating the neomorphic effects of mutant p53 in a mouse model of Li-Fraumeni Syndrome. While at MIT, he also helped develop a conditional mutant model of advanced lung adenocarcinoma. After graduating in 2005, Dr. Olive began a postdoctoral fellowship in the laboratory of David Tuveson at the University of Pennsylvania, later moving with the lab to the University of Cambridge in England. There he built a translational research facility for studying novel anticancer therapeutics in genetically engineered mouse models of pancreatic cancer. His studies into chemoresistance and the effects of Hh pathway inhibitors on drug delivery in pancreatic cancer were published in Science in 2009, and have led to multiple clinical trials to evaluate the approach in patients with metastatic pancreatic cancer. In 2010, Dr. Olive joined the faculty of the Columbia University Herbert Irving Comprehensive Cancer Center, where he has established a laboratory dedicated to translational science and experimental therapeutics in pancreatic ductal adenocarcinoma.

George Zavoico, PhD

MLV

George B. Zavoico, PhD, is Managing Director, Research, and a Senior Equity Research Analyst at MLV & Co, a boutique investment bank and institutional broker-dealer based in New York. He has over 7 years of experience as a life sciences analyst writing research on publicly traded equities. Prior to MLV, he was an equity analyst with Westport Capital Markets and Cantor Fitzgerald. Prior to working as an analyst, Dr Zavoico established his own consulting company serving the biotech and pharmaceutical industries by providing competitive intelligence and marketing research, due diligence services, and guidance in regulatory affairs. He also wrote extensively on healthcare and the biotech and pharmaceutical industries for periodicals targeting the general public and industry executives. Dr Zavoico began his career as a Senior Research Scientist at Bristol-Myers Squibb Co., moving on to management positions at Alexion Pharmaceuticals, Inc. and T Cell Sciences, Inc. (now Celldex Therapeutics, Inc.). He has a BS in Biology from St. Lawrence University and PhD in Physiology from the University of Virginia and has held post-doctoral positions at the University of Connecticut Health Sciences Center and Brigham and Women's Hospital and Harvard Medical School.

Jennifer Henry, PhD

The New York Academy of Sciences

Keynote Speaker

Dafna Bar-Sagi, PhD

NYU Langone Medical Center

Dafna Bar-Sagi, PhD, has been the senior vice president and vice dean for science, chief scientific officer of NYU Langone Medical Center since the summer of 2011. She is also a Professor of Biochemistry. One of the country's leading cancer biologists, Dr. Bar-Sagi is widely known for elucidating cellular pathways involved in controlling cell growth. She has published more than 100 peer-reviewed research papers in leading journals on the molecular mechanisms underlying tumor development, devoting considerable research to RAS proteins, essential control elements of molecular machineries that drive the neoplastic process in many human cancers. Prior to joining the Medical Center in 2006 as chair of the Department of Biochemistry, Dr. Bar-Sagi headed the Department of Molecular Genetics and Microbiology at the State University of New York (SUNY) at Stony Brook. She earned her undergraduate and master's degrees from Bar-Ilan University, Israel, and her PhD from SUNY at Stony Brook. She has been a member of many scientific advisory boards including Starr Cancer Consortium, Pancreatic Cancer Action Network, and Abramson Family Cancer Research Institute and has served on the editorial boards of multiple journals including Cancer Cell, Oncogene, and Molecular and Cellular Biology.

Speakers

Adrienne D. Cox, PhD

University of North Carolina at Chapel Hill

Adrienne D. Cox, PhD, is Associate Professor of Pharmacology and Radiation Oncology at the University of North Carolina at Chapel Hill. She was a National Merit Scholar at Pomona College, a founding student of the interdisciplinary Biomedical Sciences PhD program and a National Science Foundation Fellow at Eastern Virginia Medical School. She performed her postdoctoral studies with Channing Der in La Jolla, CA, at what is now the Sanford-Burnham Institute. Dr. Cox has extensive experience in basic and translational studies of Ras family small GTPases. Since the earliest studies of the mechanisms of action of farnesyltransferase inhibitors, she has helped to elucidate the role and importance of posttranslational modifications such as isoprenoid lipids and phosphorylation to the membrane targeting events that drive Ras family signaling specificity, and emphasized the importance of isoform differences in promoting context-dependent oncogenesis. Her focus on molecular therapeutics of pancreatic cancer is driven by these findings. A member of the Lineberger Comprehensive Cancer Center, Dr. Cox is currently Chief of the Division of Cancer Research in the Department of Radiation Oncology.

Jeffrey M. Hardacre, MD

University Hospitals Case Medical Center

Dr. Hardacre graduated from the University of Wisconsin-Madison with a BS in Molecular Biology. He received his MD from Duke University School of Medicine where he was a Howard Hughes Medical Student Research Training Fellow. He completed his surgical training at The Johns Hopkins Hospital. In 2004 he joined the Department of Surgery at University Hospitals Case Medical Center and Case Western Reserve University School of Medicine in Cleveland, OH. Currently, he is an Associate Professor of Surgery and the Section Head of Pancreatic Surgery at University Hospitals Seidman Cancer Center.

Alec C. Kimmelman, MD, PhD

Dana Farber Cancer Institute

Dr. Kimmelman is currently an Assistant Professor of Radiation Oncology at the Dana-Farber Cancer Institute at Harvard Medical School. He completed his undergraduate education at Cornell University and received his MD/PhD from the Mount Sinai School of Medicine in NY. After graduating, he completed residency training at the Harvard Radiation Oncology Program and performed his post-doctoral studies in the laboratory of Ronald A. DePinho at the Dana-Farber Cancer Institute where he identified novel genes that are important in the invasive and metastatic phenotype of pancreatic cancer. Dr. Kimmelman's lab is focused on pancreatic cancer and their recent work involves the study of the deregulation of metabolic pathways in the disease and its relation to therapeutic resistance. These studies have identified that pancreatic cancers are addicted to autophagy for continued growth and have motivated the development of two clinical trials at the Dana-Farber Harvard Cancer Center for the treatment of pancreatic cancer patients. Dr. Kimmelman is also currently an attending Radiation Oncologist at the Dana-Farber Cancer Institute and Brigham and Womens Hospital specializing in Gastrointestinal Malignancies and is the Director of Preclinical Therapeutics of the small animal microirradiator facility.

David A. Tuveson MD, PhD

Cold Spring Harbor Laboratory

David Tuveson is Professor and deputy director of the cancer centre at Cold Spring Harbor Laboratory. Dr. Tuveson obtained a bachelors degree in chemistry at MIT, followed by MD and PhD degrees at Johns Hopkins. Dr. Tuveson was a medical resident at Brigham and Women's Hospital and a medical oncology fellow at Dana-Farber/Partners Cancer Care. During his post-doctoral years in Boston, Dr. Tuveson co-developed KIT inhibitors for gastrointestinal stromal tumors with George Demetri. Simultaneously, he generated several widely-used mouse cancer models with Tyler Jacks. As an independent investigator, his lab generated the first mouse models of ductal pancreatic cancer at the University of Pennsylvania. Subsequently, Dr. Tuveson was recruited to the University of Cambridge to develop preclinical and clinical therapeutic strategies for pancreatic cancer. In Cambridge, his lab identified a variety of parameters that limit therapeutic efficacy in pancreatic cancer, including poor drug delivery and survival factors in the microenvironment. These findings are currently undergoing clinical evaluation. Dr. Tuveson was recruited back to the USA to direct the Cancer Therapeutics Initiative at CSHL and to serve as Director of Research for the Lustgarten Foundation. He continues to practice medical oncology with an adjunct appointment at MSKCC. His awards include the Rita Allen Scholarship.

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Abstracts

The high prevalence of activated forms of K-Ras in pancreatic cancer is believed to reflect the capacity of Ras-dependent signaling pathways to regulate cellular processes that are relevant to both tumor initiation and progression. A major goal of our work is to enhance the understanding of the specific roles that oncogenic K-Ras-triggered signals play in the process of pancreatic tumorigenesis, and to explore the amenability of these signals to pharmacological intervention. The talk will focus on ongoing efforts to delineate the functional contribution of oncogenic K-Ras to tumor immunity and bioenergetics.

Targeting KRAS in Pancreatic Cancer: Challenges and OpportunitiesAdrienne D. Cox, PhD, University of North Carolina at Chapel Hill

KRAS has been shown repeatedly to be a key driver of pancreatic cancer initiation and maintenance, and is therefore a critical therapeutic target for this disease. However, despite massive efforts to develop molecularly targeted agents that directly inhibit Ras itself, no clinically successful candidate drugs have been identified. Agents that interfere with Ras membrane targeting and downstream effector function are the subjects of intense investigation as potentially more tractable approaches, yet these too remain extremely challenging. Our recent development of inducible kinase tools and identification of ERK isoform-selective functions in pancreatic cancer provide new opportunities to improve therapeutic outcomes by blocking critical signaling events driven by KRAS, and these will be discussed.

Results: Seventy patients were treated with gemcitabine and 5-fluorouracil based chemoradiotherapy as well as algenpantucel-L (mean 12 doses, range 1-14). After a median follow-up of 21 months, the 12-month disease-free survival was 62%, and the 12-month overall survival was 86%. The most common adverse events were injection site pain and induration.

Pancreatic cancers have an intense resistance to currently available therapeutics which results in a dismal 5-year survival rate. This resistance points toward altered cell survival and metabolic pathways. In this regard we have previously shown that pancreatic cancers have elevated basal autophagy which is required for their continued growth. Importantly, inhibition of autophagy pharmacologically or by RNAi approaches leads to decreased oxidative phosphorylation, a drop in ATP production, and ultimately growth inhibition. These findings have implicated autophagy as a key component of pancreatic cancer metabolism and have motivated the opening of multiple clinical trials assessing the efficacy of hydroxychloroquine as an autophagy inhibitor in pancreatic cancer. Additional work from our group has demonstrated that oncogenic Kra spromotes a systematic rewiring of pancreatic cancer metabolism allowing glucose and glutamine to be utilized in a variety of biosynthetic pathways. Importantly, several of these metabolic pathways are critical for tumor growth and therefore represent potential therapeutic targets. These and other aspects of pancreatic cancer metabolism will be discussed.

Pancreatic Cancer is a deadly disease that lacks effective therapies. We have generated a mouse model of advanced pancreatic cancer and used it to investigate the response to conventional and investigational agents. Recently, we showed that that drug delivery is hampered by poor perfusion and diffusion of agents into pancreatic tumors, and devised a variety of strategies to circumvent this. Currently, we are characterizing a biological agent that attenuates the activity of Connective Tissue Growth Factor (CTGF). We find that CTGF antagonism promotes apoptosis of neoplastic cells and survival of mice when co-administered with the cytotoxic gemcitabine, without increasing the delivery of gemcitabine. The potential mechanisms of action of this approach and relevance to the clinic will be discussed.

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